Usual Timeline of Hand, Foot, and Mouth Disease
Hand, foot, and mouth disease follows a predictable course over 2-3 weeks, with fever appearing first, followed by oral lesions within 1-2 days, then the characteristic rash on hands and feet, with complete resolution typically occurring within 7-14 days of symptom onset. 1, 2, 3
Initial Phase (Days 1-2)
Fever is the first symptom, typically low-grade but can exceed 102.2°F (39°C), accompanied by malaise, sore throat, and irritability in young children. 4 This prodromal period may also include:
- Respiratory symptoms such as cough and rhinitis, especially in younger children 4
- Gastrointestinal symptoms including nausea, vomiting, and diarrhea occasionally 4
- General discomfort and reduced appetite 2
Oral Lesion Development (Days 2-3)
Painful oral ulcerations typically appear 1-2 days after fever onset, representing the first visible manifestation of disease. 2, 3 These oral lesions are usually the first clinical signs that prompt medical evaluation. 3
Rash Appearance (Days 3-5)
The characteristic exanthem develops a few days after initial symptoms, beginning as small pink macules that evolve to vesicular lesions with highly characteristic distribution on palms and soles. 4, 5 The rash may also involve:
- Maculopapular or papulovesicular eruptions on hands and feet 2
- Widespread distribution beyond classic sites in atypical presentations, involving legs, trunk, and other areas 1, 6
Resolution Phase (Days 7-14)
Lesions usually resolve completely within 7-10 days, though the atypical variant may take up to 14 days for complete resolution. 2, 6 The healing process follows this sequence:
- Fever typically resolves within the first few days 2
- Oral ulcerations heal within 7-10 days 1
- Skin lesions resolve without scarring 6
Late Manifestations (Weeks 2-8)
Periungual desquamation typically begins 2-3 weeks after fever onset, extending from the periungual region to involve palms and soles. 1 Additional late findings include:
- Beau's lines (deep transverse nail grooves) may appear 1-2 months after fever onset, representing a delayed sequela rather than active disease 1
- Onychomadesis (nail loss) can occur up to 2 months after initial symptoms, particularly with coxsackievirus A6 infections 5
Return to Activities Timeline
Children can return to daycare once fever has resolved and mouth sores have healed, even if skin rash is still present. 1 Exclusion based solely on healing skin lesions is unnecessary, as by the time HFMD is diagnosed, the child has likely been shedding virus for weeks. 1
Important Clinical Pitfalls
- Do not wait for all classic features to appear simultaneously - the clinical features are not all present at a single point in time, making early diagnosis challenging 2, 5
- Monitor for neurological complications in severe cases, particularly with enterovirus 71, which can cause encephalitis/meningitis, acute flaccid myelitis, or acute flaccid paralysis 1, 5
- Reassess after 2 weeks if lesions are not improving with standard care 1
- Re-evaluate and consider alternative diagnoses if evidence of infection has not resolved after 4 weeks 1